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Molecular dynamics study of DNA binding by INT-DBD under a polarized force field

Authors

  • Xue X. Yao,

    1. Institute of Theoretical and Computational Chemistry, Key Laboratory of Mesoscopic Chemistry of MOE, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China
    2. College of Engineering, Nanjing Agricultural University, Nanjing 210031, China
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  • Chang G. Ji,

    Corresponding author
    1. State Key Laboratory of Precision Spectroscopy, Department of Physics, Institute of Theoretical and Computational Science, East China Normal University, Shanghai 200062, China
    • State Key Laboratory of Precision Spectroscopy, Department of Physics, Institute of Theoretical and Computational Science, East China Normal University, Shanghai 200062, China

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  • Dai Q. Xie,

    1. Institute of Theoretical and Computational Chemistry, Key Laboratory of Mesoscopic Chemistry of MOE, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China
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  • John Z.H. Zhang

    Corresponding author
    1. State Key Laboratory of Precision Spectroscopy, Department of Physics, Institute of Theoretical and Computational Science, East China Normal University, Shanghai 200062, China
    2. Department of Chemistry, New York University, New York, NY 10003
    • State Key Laboratory of Precision Spectroscopy, Department of Physics, Institute of Theoretical and Computational Science, East China Normal University, Shanghai 200062, China

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Abstract

The DNA binding domain of transposon Tn916 integrase (INT-DBD) binds to DNA target site by positioning the face of a three-stranded antiparallel β-sheet within the major groove. As the negatively charged DNA directly interacts with the positively charged residues (such as Arg and Lys) of INT-DBD, the electrostatic interaction is expected to play an important role in the dynamical stability of the protein–DNA binding complex. In the current work, the combined use of quantum-based polarized protein-specific charge (PPC) for protein and polarized nucleic acid-specific charge (PNC) for DNA were employed in molecular dynamics simulation to study the interaction dynamics between INT-DBD and DNA. Our study shows that the protein–DNA structure is stabilized by polarization and the calculated protein–DNA binding free energy is in good agreement with the experimental data. Furthermore, our study revealed a positive correlation between the measured binding energy difference in alanine mutation and the occupancy of the corresponding residue's hydrogen bond. This correlation relation directly relates the contribution of a specific residue to protein–DNA binding energy to the strength of the hydrogen bond formed between the specific residue and DNA. © 2013 Wiley Periodicals, Inc.

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